Iron oxy biominerals inside protein nanocages, iron concentrates for protein synthesis and oxygen/peroxide traps for antioxidant protection, are called ferritins. Ferritin is an intracellular protein that concentrates up to 4,500 iron atoms as Fe2O3.H2O, and self-assembles from 24 subunits into a hollow protein (usually 12 nm in diameter with an 8 nm-diameter cavity) with 432 symmetry, or in bacteria (Dps or mini-ferritin protein) self-assembles from 12 subunits in a hollow protein (usually 8 nm in diameter with a 5 nm diameter cavity) with 32 symmetry. Ferritin concentrates iron in cells 100 billion times above the solubility of ferric ion in a nontoxic, accessible form. The subunits, four α-helix bundles, contain a catalytic center that converts two Fe(II) atoms to an Fe(III)-oxo bridged dimer intermediate in mineralization. The two classes of ferritins are: i) maxi-ferritins, 24-polypeptide, 4-bundle subunit assemblies found in animals, plants, and bacteria; and ii) mini-ferritins (also called Dsp proteins), 12-polypeptide, 4-bundle subunit assemblies in archaea and bacteria.
In vertebrates, a subunit (L) with an inactive catalytic center coassembles with the catalytically active subunits (H) with tissue-specific H/L ratios to modulate rapid H subunit iron uptake. The H-chain plays an essential role in the rapid biomineralization of iron for storage, while the L-chain serves in iron-core nucleation. In addition to concentrating iron, ferritin plays an important role in scavenging intracellular iron to modulate the cellular labile iron pool. The primary route of iron transit into and out of the protein is through eight hydrophilic pores in the protein shell, which lead to the ferroxidase site (1.0 to 1.5 nm away) and from the ferric oxide nanoparticle (2 nm away). Clusters of glutamate residues located at the subunit dimer interfaces on the ferritin cavity nucleate the mineral.
Reductants and chelators outside the ferritin protein gain access to the ferric mineral inside through pores, controlled by gates, in the ferretin protein nanocages. The ferritin pore gates, identified by mutagenesis and protein crystallography, are highly conserved in both maxi-ferritins and mini-ferritins, and consist of two sets of amino acid pairs: i) between C-D helices, leucine 110/leucine 134; and ii) between the B-C/C-D loops, arginine 71/aspartate 122, in each of three, folded polypeptide, 4-bundle subunits arranged around the pores.